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Gut Microbiota in Health and Diseases: The Role of Pro-/Pre-/Syn-/Post-Biotics...
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Gut Microbiota in Health and Diseases: The Role of Pro-/Pre-/Syn-/Post-Biotics in the Gut–Liver–Brain Axis

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: closed (15 June 2026) | Viewed by 29177

Editors

Dr. Mohamad Khalil

E-Mail Website
Guest Editor
Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy
Interests: polyphenols; nutritional phytochemicals; gut microbiota; metabolic disturbances; metabolism
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Piero Portincasa

grade E-Mail Website
Co-Guest Editor
Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy
Interests: lipid metabolism; enterohepatic circulation; liver steatosis; gut microbiota; polyphenols
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Introduction: The gut microbiome is a diverse array of microorganisms residing in the gastrointestinal tract, forming a complex ecosystem vital for human health. It significantly influences numerous physiological processes, including digestion, metabolism, immune function, and mental health. Notably, the gut–liver–brain axis illustrates the interconnectedness of gut microbiota, metabolic processes, and mental health.

The gut–brain axis and gut metabolic axis are intricately interconnected pathways that illustrate the complex relationship between gut health, brain function, and metabolic processes. The gut–brain axis involves bidirectional communication between the gastrointestinal tract and the central nervous system, which influences mental health. Conversely, the gut–metabolic axis focuses on how gut health impacts metabolic functions, including nutrient absorption and the production of metabolites that regulate metabolism and energy balance. These two axes are linked through various mechanisms, including the influence of gut-derived neurotransmitters on metabolic processes, the impact of stress on gut microbiota composition, and the role of chronic inflammation from gut dysbiosis in affecting both brain function and metabolic health. Understanding these connections underscores the importance of gut health in promoting overall well-being, suggesting that interventions targeting the gut may benefit both mental and metabolic health.

This Special Issue seeks to enhance our understanding of gut–microbiota–brain interaction, essential for creating effective, holistic strategies for prevention and treatment. Investigating how changes in gut microbiota can influence mental and metabolic health outcomes may lead to innovative therapeutic approaches, such as personalized probiotics or dietary adjustments aimed at fostering these issues.

We invite manuscripts that present original research, reviews, and perspectives on all aspects of gut microbiota linked with mental and metabolic health, as well as regarding biotics such as pro-/pre-/syn-/post-biotics in gut–liver–brain axis disorders. Topics of interest include, but are not limited to, the following:

  • The impact of gut-derived metabolites on liver function and overall metabolism.
  • Probiotic modulation of the gut microbiome as a strategy for mitigating and preventing mental health disorders, as supported by clinical studies.
  • The gut–liver–brain axis focuses on how changes in microbiota can alter specific pathways related to gut metabolite production and mental illness.

Dr. Mohamad Khalil
Prof. Dr. Piero Portincasa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gut microbiome
  • gut–liver–brain axis
  • gastrointestinal tract
  • digestion
  • metabolism
  • immune function

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Published Papers (4 papers)

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Research

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46 pages, 3751 KB  
Article
Gut Microbiome Modulation and Health Benefits of a Novel Fucoidan Extract from Saccharina latissima: A Double-Blind, Placebo-Controlled Trial
by Gissel Garcia, Josanne Soto, Carmen Valenzuela, Mirka Bernal, Jesús Barreto, María de la C. Luzardo, Raminta Kazlauskaite, Neil Waslidge, Charles Bavington and Raúl de Jesús Cano
Microorganisms 2025, 13(7), 1545; https://doi.org/10.3390/microorganisms13071545 - 30 Jun 2025
Cited by 6 | Viewed by 4514
Abstract
This randomized, double-blind, placebo-controlled, three-arm clinical trial evaluated the effects of a proprietary bioactive fucoidan-rich extract derived from Saccharina latissima (SLE-F) on gut microbial composition and function in healthy adults. The objective of the study was to assess the potential of SLE-F to [...] Read more.
This randomized, double-blind, placebo-controlled, three-arm clinical trial evaluated the effects of a proprietary bioactive fucoidan-rich extract derived from Saccharina latissima (SLE-F) on gut microbial composition and function in healthy adults. The objective of the study was to assess the potential of SLE-F to beneficially modulate the gut microbiome, with this paper specifically reporting on microbial diversity, taxonomic shifts, and functional pathway outcomes. Ninety-one participants received either a low dose (125 mg), high dose (500 mg), or placebo twice daily for ninety days. The primary endpoint was the microbiome composition assessed via 16S rRNA sequencing (V3–V4 region), with secondary outcomes including surveys, adverse event monitoring, and clinical evaluations. High-dose supplementation resulted in dose-dependent improvements in the microbial diversity; increased abundance of beneficial taxa, including Bifidobacterium, Faecalibacterium, and Lachnospiraceae; and reductions in inflammation-associated taxa, such as Enterobacteriaceae and Pseudomonadota. A functional pathway analysis showed enhancement in short-chain fatty acid biosynthesis and carbohydrate metabolism. The low-dose group showed modest benefits, primarily increasing Bifidobacterium, with limited functional changes. In vitro colonic simulations further demonstrated a dose-dependent increase in short-chain fatty acids and postbiotic metabolite production following SLE-F exposure. SLE-F was well tolerated, with only mild, nonspecific adverse events reported. These findings support the potential of SLE-F as a safe and effective microbiome-modulating agent, warranting further study of the long-term use and synergy with dietary interventions. Full article
(This article belongs to the Special Issue Gut Microbiota in Health and Diseases: The Role of Pro-/Pre-/Syn-/Post-Biotics in the Gut–Liver–Brain Axis)
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Review

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21 pages, 1855 KB  
Review
Emerging Role of Gut Microbiota in Modulating Response to Therapies in IBD
by Bianca Bartocci, Angelo Del Gaudio, Marco Murgiano, Alfredo Papa, Giovanni Cammarota, Antonio Gasbarrini, Franco Scaldaferri and Loris Riccardo Lopetuso
Microorganisms 2026, 14(5), 1082; https://doi.org/10.3390/microorganisms14051082 - 11 May 2026
Viewed by 626
Abstract
The gut microbiota is increasingly recognized as a key contributor in the pathogenesis and progression of inflammatory bowel disease (IBD). Compared with healthy individuals, patients with IBD show marked dysbiosis, characterized by reduced microbial diversity, an expansion of facultative anaerobes such as Proteobacteria, [...] Read more.
The gut microbiota is increasingly recognized as a key contributor in the pathogenesis and progression of inflammatory bowel disease (IBD). Compared with healthy individuals, patients with IBD show marked dysbiosis, characterized by reduced microbial diversity, an expansion of facultative anaerobes such as Proteobacteria, and a depletion of obligate anaerobes within the Firmicutes phylum. These changes have been implicated in the perpetuation of intestinal inflammation, disruption of mucosal immune homeostasis, and altered metabolic functions, further underscoring the microbiota’s relevance in IBD pathophysiology. However, microbiota-driven insights have not yet been consistently translated into therapeutic stratification or clinical decision-making. A major challenge lies in the complex and dynamic interplay between the gut microbiota and various treatment modalities, including conventional immunosuppressants, biologics, and small-molecule inhibitors. While accumulating evidence suggests that IBD treatments may modulate microbial composition and function, it remains unclear whether these changes represent a direct pharmacological effect or are secondary to inflammation control. Additionally, there is a lack of comparative data on microbiota profiles associated with differential responses to various therapeutic classes, limiting the implementation of microbiota-informed precision medicine. In this review, we synthesize current evidence on the association between gut microbiota composition and treatment outcomes, focusing on biologic agents and small-molecule therapies. Furthermore, we discuss the potential of microbiota-targeted strategies, such as fecal microbiota transplantation (FMT) and precision probiotics, in enhancing therapeutic response. A deeper understanding of host–microbe interactions could enable a more personalized and effective approach to IBD management. Full article
(This article belongs to the Special Issue Gut Microbiota in Health and Diseases: The Role of Pro-/Pre-/Syn-/Post-Biotics in the Gut–Liver–Brain Axis)
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41 pages, 2830 KB  
Review
Unraveling the Role of the Human Gut Microbiome in Health and Diseases
by Mohamad Khalil, Agostino Di Ciaula, Laura Mahdi, Nour Jaber, Domenica Maria Di Palo, Annarita Graziani, Gyorgy Baffy and Piero Portincasa
Microorganisms 2024, 12(11), 2333; https://doi.org/10.3390/microorganisms12112333 - 15 Nov 2024
Cited by 62 | Viewed by 20524
Abstract
The human gut is a complex ecosystem that supports billions of living species, including bacteria, viruses, archaea, phages, fungi, and unicellular eukaryotes. Bacteria give genes and enzymes for microbial and host-produced compounds, establishing a symbiotic link between the external environment and the host [...] Read more.
The human gut is a complex ecosystem that supports billions of living species, including bacteria, viruses, archaea, phages, fungi, and unicellular eukaryotes. Bacteria give genes and enzymes for microbial and host-produced compounds, establishing a symbiotic link between the external environment and the host at both the gut and systemic levels. The gut microbiome, which is primarily made up of commensal bacteria, is critical for maintaining the healthy host’s immune system, aiding digestion, synthesizing essential nutrients, and protecting against pathogenic bacteria, as well as influencing endocrine, neural, humoral, and immunological functions and metabolic pathways. Qualitative, quantitative, and/or topographic shifts can alter the gut microbiome, resulting in dysbiosis and microbial dysfunction, which can contribute to a variety of noncommunicable illnesses, including hypertension, cardiovascular disease, obesity, diabetes, inflammatory bowel disease, cancer, and irritable bowel syndrome. While most evidence to date is observational and does not establish direct causation, ongoing clinical trials and advanced genomic techniques are steadily enhancing our understanding of these intricate interactions. This review will explore key aspects of the relationship between gut microbiota, eubiosis, and dysbiosis in human health and disease, highlighting emerging strategies for microbiome engineering as potential therapeutic approaches for various conditions. Full article
(This article belongs to the Special Issue Gut Microbiota in Health and Diseases: The Role of Pro-/Pre-/Syn-/Post-Biotics in the Gut–Liver–Brain Axis)
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Other

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12 pages, 1128 KB  
Systematic Review
Efficacy and Safety of Probiotics in Children with Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis
by Marisa Piccirillo, Erika Renzi, Corrado De Vito, Maurizio Mennini, Giacomo Giarrusso, Giorgia Gallo, Giovanna Quatrale, Marco Bianchi, Marco Graziani, Francesca Caron, Alessandro Ferretti, Pasquale Parisi and Giovanni Di Nardo
Microorganisms 2026, 14(1), 23; https://doi.org/10.3390/microorganisms14010023 - 21 Dec 2025
Viewed by 2376
Abstract
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction (DGBI), whose exact etiology remains unclear. The “brain–gut-microbiota axis” proved to be a key target in IBS management and there is strong evidence supporting the use of probiotics for improving overall symptoms both [...] Read more.
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction (DGBI), whose exact etiology remains unclear. The “brain–gut-microbiota axis” proved to be a key target in IBS management and there is strong evidence supporting the use of probiotics for improving overall symptoms both in adults and in children. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the effects of probiotic supplementation in pediatric patients diagnosed with IBS according to Rome III or IV criteria. Scopus, PubMed, and Cochrane Library were the available databases systematically searched up to February 2025. Six RCTs with 604 participants were included in the final systematic review. Three RCTs provided data from which the meta-analysis demonstrated that probiotic supplementation has a significant effect on reducing abdominal pain in patients with IBS (SMD −0.95, 95% CI −1.63 to −0.27). Other three RCTs reported data on the effects on stool consistency, and their meta-analysis proved that supplementation results in stool consistency normalization in patients with diarrhea or constipation (OR 2.17, 95% CI 1.18 to 4). The present meta-analysis demonstrated that probiotic supplementation can reduce abdominal pain in pediatric patients with IBS and provide significant bowel habit normalization in patients with diarrhea or constipation at baseline compared to placebo. Full article
(This article belongs to the Special Issue Gut Microbiota in Health and Diseases: The Role of Pro-/Pre-/Syn-/Post-Biotics in the Gut–Liver–Brain Axis)
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